Initial perfusate purification during subnormothermic machine perfusion for porcine liver donated after cardiac death

Obara, Hiromichi; Morito, Noriyuki; Matsuno, Naoto; Yoshikawa, Ryo; Nakajo, Tetsuya; Gochi, Mikako; Otani, Masahide; Shonaka, Tatsuya; Furukawa, Hiroyuki; Hirano, Toshihiko; Enosawa, Shin

doi:10.1007/s10047-019-01123-5

Cited by 6 publications

(5 citation statements)

References 23 publications

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“…Different strategies have been established to reduce the accumulation of pro-inflammatory molecules during machine perfusion. A simple but effective idea was published by Obara et al: replacement of the initial perfusate after 5 minutes of subnormothermic machine perfusion as an attempt to mimic a filter or dialyzer led to significantly lower concentrations of transaminases and lactate levels after reperfusion in a porcine model [ 33 ]. Haemoadsorption with an incorporated cytokine filter has been used to reduce the inflammatory response during kidney machine perfusion resulting in improved renal blood flow, albeit without significantly influencing renal function [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Interleukin-18 and High-Mobility-Group-Protein B1 are Early and Sensitive Indicators for Cell Damage During Normothermic Machine Perfusion after Prolonged Cold Ischemic Storage of Porcine Liver Grafts

Beetz¹,

Cammann²,

Weigle³

et al. 2022

Transpl Int

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In the era of organ machine perfusion, experimental models to optimize reconditioning of (marginal) liver grafts are needed. Although the relevance of cytokine signatures in liver transplantation has been analyzed previously, the significance of molecular monitoring during normothermic machine perfusion (NMP) remains elusive. Therefore, we developed a porcine model of cold ischemic liver graft injury after prolonged static cold storage (SCS) and subsequent NMP: Livers obtained from ten minipigs underwent NMP for 6 h directly after procurement (control group) or after 20 h of SCS. Grafts after prolonged SCS showed significantly elevated AST, ALT, GLDH and GGT perfusate concentrations, and reduced lactate clearance. Bile analyses revealed reduced bile production, reduced bicarbonate and elevated glucose concentrations after prolonged SCS. Cytokine analyses of graft perfusate simultaneously demonstrated an increase of pro-inflammatory cytokines such as Interleukin-1α, Interleukin-2, and particularly Interleukin-18. The latter was the only significantly elevated cytokine compared to controls, peaking as early as 2 h after reperfusion (11,012 ng/ml vs. 1,493 ng/ml; p = 0.029). Also, concentrations of High-Mobility-Group-Protein B1 were significantly elevated after 2 h of reperfusion (706.00 ng/ml vs. 148.20 ng/ml; p < 0.001) and showed positive correlations with AST (r2 = 0.846) and GLDH (r2 = 0.918) levels. Molecular analyses during reconditioning of liver grafts provide insights into the degree of inflammation and cell damage and could thereby facilitate future interventions during NMP reducing acute and chronic graft injury.

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Section: Discussionmentioning

confidence: 99%

Interleukin-18 and High-Mobility-Group-Protein B1 are Early and Sensitive Indicators for Cell Damage During Normothermic Machine Perfusion after Prolonged Cold Ischemic Storage of Porcine Liver Grafts

Beetz¹,

Cammann²,

Weigle³

et al. 2022

Transpl Int

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“…This model avoids the problems caused by the heterogenous nature of discarded human liver that troubled previous researches, and is conducive to the development of preclinical studies. Obara, H et al [49,50] suggested that installation of leukocyte filter or replacement of purified perfusate in SNMP could reduce hepatic artery pressure and release the levels of AST, LDH and ALP in porcine liver donated after cardiac death. This method is expected to further improve the ischemia-reperfusion injury in ECD.…”

Section: Subnormothermic Machine Perfusion (Snmp)mentioning

confidence: 99%

Research progress on hepatic machine perfusion

Gao¹,

He²,

Xia³

et al. 2021

Int. J. Med. Sci.

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Nowadays, liver transplantation is the most effective treatment for end-stage liver disease. However, the increasing imbalance between growing demand for liver transplantation and the shortage of donor pool restricts the development of liver transplantation. How to expand the donor pool is a significant problem to be solved clinically. Many doctors have devoted themselves to marginal grafting, which introduces livers with barely passable quality but a high risk of transplant failure into the donor pool. However, existing common methods of preserving marginal grafts lead to both high risk of postoperative complications and high mortality. The application of machine perfusion allows surgeons to make marginal livers meet the standard criteria for transplant, which shows promising prospect in preserving and repairing donor livers and improving ischemia reperfusion injury. This review summarizes the progress of recent researches on hepatic machine perfusion.

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“…As the heart's metabolism decreases by 5% with each °C drop in temperature (50% reduction in the metabolic rate at 27°C compared to 37°C) it is desirable to store/transport DCD heart at lower temperatures 18 . Novel nonblood‐based perfusates such as modified UW‐MPS that incorporated polyethylene glycol (PEG‐20K) as impermeant has shown promising results in preserving DCD kidney and livers 41,42 . Another low‐pressure perfusion solution showed promising results in preserving the DCD animal and human (not transplanted) hearts 17,43 .…”

Section: Remaining Challenges To Expand Dcd Heart Transplantationmentioning

confidence: 99%

“…18 Novel nonblood-based perfusates such as modified UW-MPS that incorporated polyethylene glycol (PEG-20K) as impermeant has shown promising results in preserving DCD kidney and livers. 41,42 Another low-pressure perfusion solution showed promising results in preserving the DCD animal and human (not transplanted) hearts. 17,43 An ex situ perfusion system utilizing nonblood-based perfusate, delivered either by gravity or machine perfusion, small enough for transportation and not cost-prohibitive will advance the ex situ perfusion/transportation of DCD hearts.…”

Section: Ex Situ Perfusion Preservationmentioning

confidence: 99%

Heart transplantation from donation after circulatory death donors: Present and future

et al. 2020

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The first successful human heart transplantation was reported on 3 December 1967, by Christiaan Barnard in South Africa. Since then this life‐saving procedure has been performed in over 120 000 patients. A limitation to the performance of this procedure is the availability of donor hearts with as many as 20% of patients dying before a donor's heart is available for transplant. Today, hearts for transplantation are procured from individuals experiencing donation after brain death (DBD). Interestingly, this, however, was not always the case as the first heart transplants occurred after circulatory death. Revisiting the availability of hearts for transplant from those experiencing donation after circulatory death (DCD) could further expand the number of hearts suitable for transplantation. There are several considerations pertinent to transplanting hearts from those undergoing circulatory death. In this review, we summarize the main distinctions between DBD and DCD heart donation and discuss the research relevant to increasing the number of hearts available for transplantation by including individual's hearts that experience circulatory death.

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Initial perfusate purification during subnormothermic machine perfusion for porcine liver donated after cardiac death

Cited by 6 publications

References 23 publications

Interleukin-18 and High-Mobility-Group-Protein B1 are Early and Sensitive Indicators for Cell Damage During Normothermic Machine Perfusion after Prolonged Cold Ischemic Storage of Porcine Liver Grafts

Interleukin-18 and High-Mobility-Group-Protein B1 are Early and Sensitive Indicators for Cell Damage During Normothermic Machine Perfusion after Prolonged Cold Ischemic Storage of Porcine Liver Grafts

Research progress on hepatic machine perfusion

Heart transplantation from donation after circulatory death donors: Present and future

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